Prostate cancer (PCa) is the most common cancer in American men and is the second leading cause of cancer death. Progress in treating human prostate cancer has been hampered by the finding that histologically identical cancers can exhibit widely variant clinical behavior. For example, in some men diagnosed with prostate cancer, the disease progresses slowly with a prolonged natural history while in other patients, disease progression can be rapid and definitive local therapy can be ineffective.
Improved early detection has resulted in more men being diagnosed with localized prostate cancer (PCa); however, the clinical course of disease after diagnosis is heterogeneous, with recurrence observed in up to one third of patients, even after radical prostatectomy (RP). Therefore, approximately 60% of men diagnosed with low-risk choose to undergo RP as their primary treatment. However, RP may carry potential side effects affecting quality of life, such as incontinence and impotence if nerve-sparing surgery is not possible. Brachytherapy and external-beam radiotherapy are also options for treatment, a choice of primary treatment for approximately 15% of low-risk patients. “Active surveillance” or “watchful waiting” are options that are least favored by most patients, with approximately only ˜10% of patients choosing active surveillance in the US. Delayed treatment would be desirable for men with low-risk disease who may have a tumor that will not progress further in order to reduce the negative impact of side effects on health related quality of life. It is reported that approximately 30% of patients who elect for radical prostatectomy have truly low risk of disease recurrence and may benefit more if they opt for “active surveillance” (AS). In contrast, men classified as high risk for PCa-related mortality would benefit from being aggressively treated for their disease at the time of diagnosis, instead of waiting for evidence of disease recurrence to occur. All other patients should undergo and remain on AS unless signs of cancer progression force for definitive local therapy. The PIVOT trial, the first randomized trial comparing men in watchful waiting to men who underwent radical prostatectomy with at least 12 years of follow-up, showed that while only a subgroup of men can benefit from RP, there were no differences seen in risk of metastasis and PCa-related mortality between the groups after 7-9 years of follow-up. Although clinical variables such as Gleason score at biopsy, patient age, PSA level, PSA kinetics (how quickly PSA rises over time), tumor grade and volume have been studied as possible predictors, at this point, no conclusive predictors of PCa progression have been determined.
Even after a radical prostatectomy, up to one third of patients can experience a biochemical recurrence (BCR) (also called PSA recurrence) when serum PSA levels become detectable again. Reports show that 18% to 29% of individuals with BCR can progress to metastatic disease, indicating that BCR is suggestive and not definitive of possible aggressive disease. Therefore, identifying patients at risk of recurrence after RP is also desirable in order to treat them more aggressively after surgery.
Overall, current tools available to determine prognosis for localized PCa patients have limited predictive accuracy. These tools include models and nomograms, intended for easy application in the clinic, that use a combination of clinical variables such as biopsy Gleason score, clinical stage, pre-operative PSA level, and in some models data collected at time of surgery.